Biochemical Properties of Cholinesterases

The cholinesterases, as indicated by the name, hydrolyze the esters of choline. However, the specificity for choline esters is not absolute, as evidenced by the hydrolysis of other esters, albeit at a slower rate. While acetylcholinesterase has high specificity not only for acetylcholine— CH3C00(CH2)2N+(CH3)3—but also for acetylthiocholine and other acetyl esters, most plasma cholinesterases catalyze the hydrolysis of butyrylcholine, butyrylthiocholine, and other butyryl esters at faster rates than the corresponding acetyl derivatives. With some homologous esters of acetylcholine, it was shown early on (DIO) that butyrylcholine 

The introduetion of a double bond at the a, 3 position in the alkyl group of choline esters reduces the rate of hydrolysis of the ester compared with that of the corresponding saturated alkyl ester. A double bond at any other position appears to have a less predictable effect, e.g., 4-pentenoylchoIine—CH2 = CH(CH2)2COO(CH2)2N+(0113)3—is hydrolyzed faster than is vinylacetylcholine—CH2 = CHCH2COO 

Beckett and his co-workers (B14) examined the hydrolysis by purified horse serum cholinesterase of a number of analogs of butyrylcholine. The introduction of an a-methyl group into the choline moiety of the butyryl ester was found to decrease the rate of enzymic hydrolysis only slightly, whereas a drastic reduction was found for d-methyl substitution. The substitution of various functional groups into the butyryl moiety of butyrylcholine modified the affinity of the substrate for the enzyme. These results are summarized in Table 3. Since values can be assumed to be inversely proportional to affinity values, the results shown in this table indicate that j8-hydroxyl substitution increases the affinity of the substrate for the enzyme, and a,/3-unsaturation effects even greater affinity. Acetoacetylcholine has a greater affinity for the enzyme surface 

THE Hydrolysis of Butyrylcholine and Some Analogs by Purified Horse Serum Cholinesterase  

The kinetics of hydrolysis of lactoylcholine—CH3CH(OH)COO(CH2)2 N+(0113)3—and its isomers were studied by Sastrey and White (S3). The rationale for this study stemmed from the possible formation of lactoylcholine from propionylcholine—CH3CH2COO(CH2)2N+ (0113)3—or acrylylcholine—OHLj = CHOOO(OH2)2N+(0113)3—both of which have been isolated from animal tissues (B3, W24). DL-Lactoylcholine was found to be hydrolyzed by cholinesterase at a rate three to four times faster than acetylcholine, but in contrast to acetylcholinesterase, the plasma enzyme did not differentiate between the n- and L-enantiomorphs of lactoylcholine. 

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